Electrosynthesis of organic compounds

ABSTRACT

Disclosed is a process for the electrochemical transformation of a compound to form a product, the process comprising (i) effecting the transformation in the presence of an electrolyte comprising at least one room temperature ionic liquid, wherein the ionic liquid is air-stable and moisture-stable, (ii) recovering the product, and optionally (iii) recovering the ionic liquid. The process can be used to effect the electrochemical transformation of a wide range of organic compounds.

This invention relates to electrochemical transformations of organiccompounds in ionic liquids. The present invention is primarily concernedwith oxidation and/or reduction of the organic compound to produce anon-polymeric product.

Electrosynthesis, i.e. synthesis of organic compounds by electrochemicalprocedures, provides an attractive alternative to conventional methodsused for conducting synthetic organic chemistry. Electrochemicalprocedures can be used to achieve a clean and complete conversion of astarting material to product without using hazardous or toxicexperimental conditions.

Traditionally, electrosynthetic reactions are usually carried out inmolecular solvents (both aqueous and non-aqueous); these solventsusually contain a supporting electrolyte to enhance the intrinsicallypoor electrochemical properties (e.g., low conductivity) of molecularsolvents. The use of a supporting electrolyte may add significantly tothe cost of the process and has the further disadvantage that it mayrequire an additional purification step to separate it from the product.

Ionic liquids are a class of solvents which, unlike conventionalmolecular solvents, are completely ionised. Molten alkali metal halidesalts (e.g. molten sodium chloride) are typical ionic liquids. Ingeneral, molten salts are thought of as possessing high melting pointsand being highly corrosive. However, this is not always the case.

The term “ionic liquid” refers to a liquid that is capable of beingproduced by melting a solid, and when so produced, consists solely ofions. Ionic liquids may be derived from organic salts, especially saltsof heterocyclic nitrogen-containing compounds.

Ionic liquids may be regarded as consisting of two components, which area positively charged cation and a negatively charged anion. An ionicliquid may be formed from a homogeneous substance comprising one speciesof cation and one species of anion, or can be composed of more than onespecies of cation and/or anion. Thus, an ionic liquid may be composed ofmore than one species of cation and one species of anion. An ionicliquid may further be composed of one species of cation, and one or morespecies of anion.

The term “ionic liquid” as used herein may refer to a homogeneouscomposition consisting of a single salt (one cationic species and oneanionic species) or it may refer to a heterogeneous compositioncontaining more than one species of cation and/or more than one speciesof anion.

The term “ionic liquid” includes compounds having both high meltingtemperature and compounds having low melting temperatures. Organic saltsoften have much lower melting points, in many cases below 373 K. Thus,many organic salts have melting temperatures of less than 100° C. Someorganic salts have melting temperatures well below 0° C.

The term “room temperature ionic liquid” is used to describe a class ofionic liquids having melting temperatures at or below room temperature.Thus, such ionic liquids may have melting temperatures below about 40°C., preferably below about 35° C. and even more preferably, below about25° C. Typical melting temperatures may range from −50° C. to 30° C.,preferably −20° C. to 25° C. and more preferably −10° C. to 25° C.

A feature of room temperature ionic liquids is that they haveparticularly low (essentially zero) vapour pressures. Additionally,ionic liquids generally remain liquid over a large temperature range.

One of the first examples of a room temperature ionic liquid isethylammonium nitrate. U.S. Pat. Nos. 2,445,331, 2,446,349 and 2,446,350describe the use of mixtures of aluminium halides and N-alkylpyridiniumhalide salts for electrodepositing aluminium. However, the air- andmoisture-sensitivity of ionic liquids containing aluminium halideslimited their use as solvents. Although ionic liquids have been employedin the synthesis of organic compounds, there are, however, very fewexamples of electrochemical synthesis using ionic liquids.

R. T. Carlin & P. C. Truelove, Electrochimica Acta, 37 (1992) 2615-2628,G. T. Cheek & R. A. Osteryoung, J. Electrochem. Soc., 129 (1982)2488-2496, M. Lipsztajn & R. A. Osteryoung, Inorg. Chem., 24 (1985)716-719 and C. L. Hussey & L. A. King, in Proceedings of theElectrochemical Society: Second International Symposium on Molten Salts,Vol. PV 81-10, J. Braunstein & J. R. Selman (Eds), The ElectrochemicalSociety, Inc, Pennington N.J. (1981) describe electrochemical studies inionic liquids. However, these references do not disclose the use ofionic liquids in synthetic applications to produce organic compounds. Inthe electrochemical studies, no details are provided as to whether orhow a product may be isolated. Thus, the application of this technologyto molecular electrosynthesis remains largely unexplored.

Most of the examples of the use of ionic liquids in synthesis to dateare concerned with electropolymerisations. For example, J. S. Tang, & R.A. Osteryoung, Syn. Met., 45 (1991), 1-13 discloses the formation ofpolyaniline by electrochemical oxidation in a mixture of aluminiumchloride and 1-methyl-3-ethylimidazolium chloride. The polyaniline isdeposited as a film on an electrode.

G. T. Cheek, & R. B. Herzog, in Proceedings of the ElectrochemicalSociety: fourth international symposium on molten salts, Vol. PV 84-2,M. Blander, D. S. Newman, M.-L. Saboungi, G. Mamantov & K. Johnson(Eds), The Electrochemical Society, Inc., Pennington N.J., (1984)discloses the electrochemical reduction of aromatic ketones in1-methyl-3-butylimidazolium chloroaluminate systems. The products areisolated by hydrolysis of the melt with water, followed by extraction.The ionic liquid is thus destroyed in this process and cannot thereforebe reused.

J. E. Coffield & G. Mamantov, J. Electrochem. Soc., 138 (1991) 2543-2549and J. E. Coffield & G. Mamantov, J. Electrochem. Soc., 139 (1992)355-359 respectively disclose the electrochemical reduction of phenazineand perylene in basic mixtures of AlCl₃ and 1-ethyl-3-methylimidazoliumchloride or neat 1-ethyl-3-methylimidazolium hydrogen dichloride[emim][HCl₂]. The ionic liquids employed are moisture sensitive and aredestroyed in the aqueous work-up.

Thus, a particular disadvantage of the prior art procedures discussedabove is that the ionic liquids employed are air- and moisture-sensitiveionic liquids based on mixtures of aluminium chloride (or itsderivatives). These react with water to form hydrochloric acid,chloroxoaluminates and chlorohydroxoaluminates. The ionic liquid[emim][HCl₂] is also prone to evolve hydrochloric acid in the presenceof atmospheric moisture. Such solvents have obvious drawbacks in thattheir preparation, handling and storage must be done under an inertatmosphere (e.g. by the use of Schlenk apparatus or a glove box). Inaddition, product isolation is usually carried out by quenching theionic liquid with water. Such isolation is disadvantageous in thathydrochloric acid may be generated and importantly, the ionic liquid isdestroyed and thus cannot be reused.

N. L. Weinberg, A. Kentaro Hoffmann and T. B. Reddy, Tet. Lett, 12 (25)1971, 2271-2274 discloses the electrochemical reductive carboxylation ofbenzalaniline in molten tetraethyl ammonium p-toluenesulfonate.Tetraethyl ammonium p-toluenesulfonate has a high melting point, so itis necessary to conduct the reaction at a temperature of 140° C. The useof a high melting ionic liquid has its drawbacks since it is necessaryto maintain the high temperature to keep the reaction mixture in theliquid phase. In the disclosed process, the product is isolated bypouring the catholyte into cold water and extracting the aqueoussolution with trichloromethane. This document does not suggest the reuseof the ionic liquid, but because tetraethyl ammonium p-toluenesulfonateis highly soluble in water, it is necessary to remove the largequantities of water before it can be reused. Furthermore, sincetetraethyl ammonium p-toluenesulfonate is hygroscopic, it must behandled in anhydrous conditions.

Air- and moisture-stable room temperature ionic liquids are known [see,e.g. J. S. Wilkes & M. J. Zoworotko, J. Chem. Soc. Chem. Comm. (1992),965-967, J. D. Holbrey & K. R. Seddon, Clean Products and Processes, 1,(1999), 223-236, T. Welton, Chem. Rev., 99, (1999), 2071-2083, and P.Bonhote, A.-P Dias, N. Papageorgiou, K. Kalyanasundaram & M. Graltzel,Inorg. Chem. 35 (1996), 1168-1178)].

Typical cations found in room temperature ionic liquids includeN-alkylpyridinium, N,N′-dialkylimidazolium, tetraalkylammonium, andN,N-dialkylpyrrolidinium. Typical anions include chloride, nitrate,ethanoate, hexafluorophosphate, tetrafluoroborate, triflate, triflimide,and trifluoro-ethanoate.

Since the introduction of air- and moisture-stable ionic liquids, theuse of ionic liquids in a number of organic synthetic processes havebeen investigated. Examples of such processes include acylative cleavageof ethers, alkylation, amidocarbonylation, catalytic cracking, theDiels-Alder reaction, 1,3-dipolar cycloaddition, dimerization, enzymaticcatalysis, epoxidation, hydrodimerization, the Friedel-Crafts reaction,the Heck coupling, hydrogenation, multiphase bioprocessing, oxidation ofaromatic aldehydes and polymerization. U.S. Pat. No. 6,274,026 disclosesthe use of ionic liquids in the treatment of naphtha by electrochemicaloligomerisation of sulfur compounds at temperature ranges of 0-200° C.The polymeric sulfur compounds are deposited onto the anode. Eventually,the anode must be replaced.

To date, the electrosynthesis of a non-polymeric organic compound in aroom temperature air- and moisture-stable ionic liquid which can berecovered without destroying the ionic liquid has not been reported.

It is therefore an object of the present invention to overcome at leastsome of the disadvantages with prior art processes. A further object ofthe present invention is to provide a process in which the ionic liquidcan be recovered and reused.

Accordingly, one aspect of the present invention provides a process forthe electrochemical transformation of a compound to form a product, saidprocess comprising the steps of:

-   (i) effecting said transformation in the presence of an electrolyte    comprising at least one room temperature ionic liquid, said ionic    liquid being air-stable and moisture-stable, and-   (ii) recovering the product.

The use of an air- and moisture-stable room temperature ionic liquid ina process for electrochemical transformation of a compound in accordancewith the present invention is particularly advantageous overconventional solvents typically used in electrochemical experiments.Thus, their polar nature allows them to dissolve large concentrations ofa wide variety of organic and inorganic compounds. Furthermore, theionic liquids employed in the present invention have extremely largeelectrochemical windows, in certain cases over five volts. Additionally,as they are completely ionised, the need for a supporting electrolyte iseliminated.

As indicated above, the term “room temperature ionic liquid” for thepurpose of the present invention means that the ionic liquid has amelting temperature at or below room temperature. Thus, such ionicliquids may have melting points below about 40° C., preferably belowabout 35° C. and even more preferably, below about 25° C. Typicalmelting points may range from −50° C. to 30° C., preferably −20° C. to25° C. and more preferably −10° C. to 25° C. Preferably, for the purposeof the present invention, the ionic liquid electrolyte is liquid at atemperature of 28° C. or lower.

Since the ionic liquid employed in the present process is air- andmoisture-stable, the reactions can be carried out under more robustconditions and at lower temperatures and the recovery of the product canbe effected without the destruction of the electrolytic medium. Thus, ina preferred embodiment of the present process, the ionic liquid isrecovered from the reaction mixture.

The electrochemical transformation of the compound is preferably anoxidation, reduction, or a coupled pair of oxidation and reduction. Itwill be appreciated that the present process can be applied to theelectrochemical transformation of a wide variety of organic substrates.Thus, compounds that can be employed in the present process may includethose comprising at least one structural element selected from thefollowing: a carbon-halogen bond, a C═C double bond, a C≡C triple bond,an ester group, an ether group, a carboxylic acid group, an amino group,an amido group, an imido group, —OH, —NO₂, —C≡N, an aldehyde group and aketo group, and wherein said structural element is oxidized or reduced.

Typical reactions in which the structural element is reduced involve theaddition of one or more hydrogen atoms. Examples of such reactionsinclude:

-   -   conversion of keto groups >C═O to alcohol groups —C(H)(OH),    -   conversion of keto groups >C═O to methylene groups —CH₂—,    -   conversion of aldehyde groups —CHO to alcohol groups —C(H)(OH),    -   conversion of aldehyde groups —CHO to methylene groups —CH₂,    -   conversion of alkynyl groups —C≡C—to alkenyl groups >C═C<,    -   conversion of alkenyl groups >C═C< to alkyl groups >C—C<,    -   conversion of imido groups >C═NH to amino groups >CH—NH₂,    -   conversion of cyano groups —C≡N to amino groups >CH—NH₂,    -   conversion of a nitro group —NO₂ to amino groups —NH₂.

Preferred compounds for use in the present process include thosecomprising at least one structural element selected from the following:a carbon-halogen bond, a C═C double bond, an ester group, a carboxylicacid group, an amino group, an amido group, an imido group, NO₂, analdehyde group and a keto group.

The present invention is particularly useful for the electrochemicaltransformation of compounds comprising at least one structural elementselected from the following: NO₂, an imido group, an aldehyde group anda carboxylic acid group.

Particular examples of electrochemical transformations include:

-   -   the oxidative nitration of aryl compounds to nitro-aryl        compounds

-   -   -   R=alkyl, O-alkyl, NH₂, CN, etc            an example of this is the production of nitrobenzene from            benzene:

-   -   the reduction of nitro-aryl compounds to amino-aryl compounds

-   -   -   R=alkyl, O-alkyl, NH₂, CN, etc            an example of this is the production of aniline from            nitrobenzene:

-   -   the reduction of benzoic acids to benzaldehydes and/or benzyl        alcohols

-   -   -   R=alkyl, O-alkyl, NH₂, CN, etc            an example of this reaction is the conversion of anisic acid            to anisaldehyde and/or anisyl alcohol

The room temperature ionic liquid may be composed of any combination ofcation or anion which forms a liquid at room temperature and is stablein the presence of oxygen (i.e. air-stable) and moisture.

It will be appreciated that both the role of the cation and the anionare important factors in determining whether the ionic liquid is air ormoisture stable. Thus, if either the anion or cation react with air ormoisture, the ionic liquid will not be air or moisture stable. Thus, inthe case of the prior art chloroaluminate-anion based ionic liquids, thereactivity of the chloroaluminate species to air and moisture means thatthe resulting ionic liquid is unstable to air and moisture.

Preferred air- and moisture-stable room temperature ionic liquids foruse in the present invention include those comprising an imidazolium,pyridinium, pyridazinium, pyrazinium, oxazolium, triazolium, pyrazolium,pyrrolidinium, piperidinium, tetraalkylammonium or tetraalkylphosphoniumsalt. Especially preferred are ionic liquids comprising an imidazolium,pyridinium, pyridazinium, pyrazinium, oxazolium, triazolium, pyrazolium,pyrrolidinium or piperidinium salt. Particularly preferred ionic liquidsfor use in the process of the present invention comprise an imidazolium,pyridinium or pyrrolidinium salt.

Especially preferred ionic liquids include those selected from thefollowing:

wherein

-   -   each R^(a) is independently selected from a C₁ to C₄₀ straight        chain or branched alkyl or a C₃ to C₈ cycloalkyl group, wherein        said alkyl or cycloalkyl group which may be substituted by one        to three groups selected from: C₁ to C₆ alkoxy, C₆ to C₁₀ aryl,        CN, OH, NO₂, C₁ to C₃₀ aralkyl and C₁ to C₃₀ alkaryl;    -   each R^(b), R^(c), R^(d), R^(e), R^(f), R^(g) and R^(h) can be        the same or different and are each independently selected from H        or any of the R^(a) groups as defined above; and    -   [A]^(n−) represents an anion having a charge n⁻; wherein n may        be 1-3.

Within this group of ionic liquids, the following are preferred:

wherein [A]^(n−), R^(a)-R^(h) and n are as defined above.

Further preferred ionic liquids are those selected from the followingformulae:

wherein [A]^(n−), R^(a)-R^(h) and n are as defined above.

Even more preferred ionic liquids for use in the present process arethose having the following formula:

wherein [A]^(n−), R^(a), R^(b), R^(c), R^(d), R^(e), R^(g) and n are asdefined above.

Good results have been obtained with 1,3-dialkylimidazolium cation-basedionic liquids, i.e. those of formula:

wherein [A]^(n−), R^(a), R^(g) and n are as defined above.

In the above formulae, each R^(a) preferably represents C₁ to C₄₀, morepreferably C₁ to C₂₀, straight chain or branched alkyl. Especiallypreferred are those wherein each R^(a) represents C₁ to C₈ straightchain or branched alkyl group.

In the above formulae, R^(g) and R^(h) preferably each represents C₁ toC₄₀, preferably C₁ to C₂₀, straight chain or branched alkyl. Especiallypreferred are those wherein R^(g) and R^(h) represents C₁ to C₈ straightchain or branched alkyl.

Also preferred are ionic liquids of any the above formulae whereinR^(b), R^(c), R^(d), R^(e), R^(f), R^(g) and R^(h) each representshydrogen.

Further preferred are ionic liquids of any of the above formulae whereinR^(a), R^(g) and R^(h) each represents C₁-C₄₀, preferably C₁-C₂₀ andmore preferably C₁-C₈ alkyl.

The group [A]^(n−) in the above formulae preferably represents a singlespecies of anion A having valency n.

In the above formulae, n is preferably 1.

In the above formulae, [A]^(n−) preferably represents an anion selectedfrom [Cl]⁻, [Br]⁻, [I]⁻, boron or phosphorus fluorides, [NO₃]⁻, [SO₄]⁻,[HSO₄]⁻, [HCO₃]⁻, [(CF₃SO₂)₂N]⁻, [AsF₆]⁻, [SbF₆]⁻, aryl sulfonates,alkylsulfonates, mono- or difluorinated alkyl sulfonates includingperfluorinated alkylsulfonates, carboxylic acid anions, fluorinatedcarboxylic acid anions and metal halides.

Other anions include those based on [AsF₆]⁻, [SbF₆]⁻, [PF₆]⁻ and [BF₄]⁻,wherein one or more of the fluorine atoms are substituted by C₁ to C₂₀(preferably C₁ to C₈) straight chain or branched alkyl, such as methyl,ethyl, propyl and butyl.

Of these, [Cl]⁻, [Br]⁻, [I]⁻, boron or phosphorus fluorides, [NO₃]⁻,[SO₄]⁻, [HSO₄]⁻, [HCO₃]⁻, [(CF₃SO₂)₂N]⁻, [AsF₆]⁻, [SbF₆]⁻,alkylsulfonates, mono- or difluorinated alkyl sulfonates includingperfluorinated alkylsulfonates, carboxylic acid anions, fluorinatedcarboxylic acid anions and metal halides are preferred.

Especially preferred are ionic liquids of the above formulae wherein[A]^(n−) represents an anion selected from [PF₆]⁻, [BF₄]⁻, [OSO₂CF₃]⁻,[OSO₂(CF₂)₃CF₃]⁻, [(CF₃SO₂)₃C]⁻, [CH₃CH₂SO₃]⁻, [OCO₂CF₃]⁻,[OCO₂(CF₂)₃CF₃]⁻, [OCO₂CH₃]⁻, nitrate, sulfate, hydrogensulfate,hydrogencarbonate, acetate, trifluoroacetate, lactate, [(CF₃SO₂)₂N]⁻,[B(alkyl)₄]⁻ wherein each alkyl can be the same or different and can beany straight chain or branched C₁ to C₁₀ alkyl group, [SbF₆]⁻ and[AsF₆]⁻.

Ionic compounds of the above formulae wherein [A]^(n−) represents ananion selected from [PF₆]⁻, [BF₄]⁻, [OSO₂CF₃]⁻, [OSO₂(CF₂)₃CF₃]⁻,[OCO₂CF₃]⁻, [OCO₂(CF₂)₃CF₃]⁻, [OCO₂CH₃]⁻, [(CF₃SO₂)₂N]⁻, [B(alkyl)₄]⁻wherein each alkyl can be the same or different and can be any straightchain or branched C₁ to C₁₀ alkyl group, [SbF₆]⁻ and [AsF₆]⁻ are alsopreferred, with [PF₆]⁻, [BF₄]⁻ and [(CF₃SO₂)₂N]⁻ being especiallypreferred.

Particularly preferred ionic liquids are 1-butyl-3-methylimidazoliumhexafluorophosphate or N-butyl-N-methyl-pyrrolidiniumbis(trifluoromethanesulfonyl)imide.

Other air-and moisture-stable room temperature ionic liquids which areparticularly suitable for the present process include the following:

-   1-butyl-3-methylimidazolium hexafluorophosphate (bmimPF₆),-   1-hexyl-3-methylimidazolium hexafluorophosphate (C₆mimPF₆),-   1-octyl-3-methylimidazolium hexafluorophosphate (C₈mimPF₆),-   1-decyl-3-methylimidazolium hexafluorophosphate (C₁₀mimPF₆),-   1-dodecyl-3-methylimidazolium hexafluorophosphate (Cl₂mimPF₆),-   1-ethyl-3-methylimidazolium bis((trifluoromethyl)sulphonyl)amide    (emimNTf₂),-   1-hexyl-3-methylimidazolium bis((trifluoromethyl)sulphonyl)amide    (C₆mimNTf₂),-   1-hexylpyridinium tetrafluoroborate (C₆py BF₄),-   1-octylpyridinium tetrafluoroborate (C₈py BF₄), and-   1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF₄).

Air- and moisture-stable room temperature ionic liquids can generally beclassed as being hydrophilic or hydrophobic depending upon theirmiscibility with water. Thus, a hydrophilic ionic liquid is one which iscompletely miscible with water, whereas a hydrophobic ionic liquid isone which is substantially immiscible with water. By substantiallyimmiscible, it is meant that up to 10% by volume, preferably up to 5% byvolume, and even more preferably up to 1% by volume, water can dissolvein the ionic liquid to form a single phase. Typically, the amount ofwater that can be dissolved in the hydrophobic ionic liquid is 0-2% byvolume, although 0-0.5% by volume is preferred).

Many electrochemical reactions require the presence of protons.Generally, most room temperature ionic liquids are aprotic, i.e., theydo not contain free protons. Thus, it may be necessary to add a protonsource depending upon the electrochemical transformation to be effected.Typically, the proton source is selected from phenol, a mineral acid, anorganic acid, a conjugate acid (H[A]) of the anion A, or water. Ofthese, phenol, HCl, HNO₃, HBF₄, CH₃COOH and water are preferred, withphenol being especially preferred.

Although the ionic liquid electrolyte medium is liquid at roomtemperature, the electrochemical transformation need not take place atroom temperature. Although it is preferred that the electrochemicaltransformation is conducted at ambient temperatures (e.g. up to 40° C.,preferably up to 35° C., even more preferably up to 25° C.—with rangesof—10° C. to 25° C. and 0° C. to 25° C. being especially preferred), theelectrochemical transformation can be conducted at any temperature thatis within the molten range of the electrolyte and which is mostappropriate for the highest and most selective yield of the desiredproduct.

Advantageously, the present process provides the facile separation of adesired product of the electrochemical transformation from the reactionmixture. The separation may typically involve solvent extraction,distillation, precipitation or decantation of the product or ionicliquid layer if the product is immiscible with the ionic liquid.

A further advantage of the present process is that the air- andmoisture-stable room temperature ionic liquid employed in the presentinvention is not destroyed by the addition of water, and can be easilyrecovered from the reaction mixture, thus offering the possibility ofrecycling and reuse of the ionic liquid.

Thus, when an air- and moisture stable room temperature ionic liquidthat is substantially immiscible with water is employed as anelectrolyte, the product may be extracted from ionic liquid in anaqueous phase. The ionic liquid may then be used, either directly orafter treatment (e.g. to remove small amounts of water or proton donor).Unlike tetraethylammonium p-toluenesulfonate which is not a roomtemperature ionic liquid, it is possible to reuse the ionic liquidsemployed in the present invention directly, i.e. without furthertreatment, even if trace amounts of water are present. For example, thewater present may act as a proton donor, thus obviating the need for theseparate addition of a proton donor.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be described in more detail by way of the followingfigures and examples:

FIG. 1: Schematic design of an electrochemical cell typically employedin organic electrosynthesis: (A) electrical power source; (B) cell top;(C) purge gas inlet; (D) cell vessel; (E) cathode; (F) catholyte; (G)cell membrane; (H) anolyte; (I) anode.

FIG. 2: Cyclic voltammogram recorded at a glassy carbon disk electrodein a 0.205 mol L⁻¹ solution of N-methylphthalimide in the [bmim][PF₆]ionic liquid at 298 K. The scans were initiated from −1.0 V toward morecathodic potentials with v=0.040 V s⁻¹.

FIG. 3: Cyclic voltammograms recorded at a glassy carbon disk electrodein solutions of [bmim][PF₆] ionic liquids at 298 K containing: (A) 1.0mol L⁻¹ phenol; (B) 0.10 mol L⁻¹ N-methylphthalimide; (C) 1.0 mol L⁻¹phenol and 0.10 mol L⁻¹ N-methylphthalimide. The scans were initiatedfrom −1.0 V toward more cathodic potentials with v=−0.040 V s⁻¹.

FIG. 4: Cyclic voltammograms recorded at a glassy carbon disk electrodein solutions of [bmim][PF₆] ionic liquids at 298 K containing 0.063 molL⁻¹ N-methylphthalimide and 0.63 mol L⁻¹ phenol: (A) a prior toelectrolysis; (B) following electrolysis at an applied potential of −1.7V (Q=126.0 C).

FIG. 5(A): HPLC analysis of [bmim][PF₆] ionic liquid solution containing0.61 mol L⁻¹ phenol (Retention Time [RT]=7.1 min), 0.064 mol L⁻¹N-methylphthalimide (RT=11.8 min) and 0.063 mol L⁻¹N-methylhydroxyisoindol-1-one (RT=4.3 min) (standard).

FIG. 5(B): HPLC analysis of [bmim][PF₆] ionic liquid solution (RT=1.6min) containing 0.62 mol L⁻¹ phenol (RT=7.3 min), 0.065 mol L⁻¹ N-methylphthalimide (RT=12.4 min) (before reaction).

FIG. 5(C): HPLC analysis of [bmim][PF₆] ionic liquid (RT=1.4 min)solution initially containing 0.063 mol L⁻¹ N-methylphthalimide and 0.63mol L⁻¹ phenol, following electrolysis at an applied potential of −1.7 V(Q_(T)=126.0 C).

The following example illustrates a process for the reduction ofN-methylphthalimide wherein the reaction medium is1-butyl-3-methylimidazolium hexafluorophosphate.

EXAMPLE

Electrochemical synthesis was carried out in the air- andmoisture-stable room-temperature ionic liquid,1-butyl-3-methylimidazolium hexafluorophosphate [bmim][PF₆]. Thereduction of N-methylphthalimide was investigated at glassy carbonelectrodes. Cyclic voltammetric experiments indicate that the imide isreduced in two single-electron reductions. In the presence of phenol,the reduction of the imide takes place at a more anodic potential andoccurs in a single two-electron step. Exhaustive electrolysis ofN-methylphthalimide was carried out in an electrochemical cell (FIG. 1)at a glassy carbon cathode in the presence of phenol.3-hydroxy-2-methyl-isoindolin-1-one was isolated as the product(Equation [1]).

Two typical cyclic voltammograms recorded in a 0.205 mol L⁻¹ solution ofN-methylphthalimide in the [bmim][PF₆] ionic liquid at a glassy carbondisk electrode are shown in FIG. 2. For these voltammograms, thepotential was initially held at −1.0 V at which no electrochemicalreaction takes place and then lowered at a constant rate toward morecathodic potentials; at the switching potential, E_(λ), the scan wasreversed and the potential raised until it had reached the initialpotential. Potentials less than −2.4 V were avoided to avoid reductionof the ionic liquid. For E_(λ)≧−2.0 V, the voltammogram exhibited asingle reduction wave on the forward scan with a peak cathodic potentialE_(p) ^(c)=−1.78 V and a single oxidation wave on the reverse scan witha peak anodic potential E_(p) ^(a)=−1.71 V. These waves are attributedto the reversible reduction of the imide to a radical anion (Equation[2]).R+e⁻

R^(•−)  [2]

As E_(λ) is made more cathodic, a second reduction wave with E_(p)^(c)=−2.10 V becomes evident. There is no oxidation wave associated withthis second reduction wave. This reduction wave is attributed to thereduction of the imide radical anion to a di-anion (Equation [3]).R^(•−)+e⁻

R²⁻  [3]

The absence of an oxidation wave on the return sweep is an indicationthat the di-anion is highly reactive and undergoes a chemical reactiontransforming into an electrochemically inert species following theelectrochemical reduction. This probably occurs through protonation bythe acidic proton of the [bmim] cation.

In electrochemical reductions that require protonation of the product,phenol is often used as a proton donor. The addition of phenol markedlyalters the redox behaviour of the imide, as demonstrated in FIG. 3.

Voltammogram A was recorded in a 0.8 mol L⁻¹ solution of phenol in[bmim][PF₆]. This voltammogram shows that phenol is electrochemicallyinactive at potentials greater than −2.15 V. Voltammogram B was recordedin a 0.10 mol L⁻¹ solution of N-methylphthalimide in [bmim][PF₆], and issimilar to those voltammograms in FIG. 1. The reduction wave for theloss of the first electron has E_(p) ^(c)=−1.79 V and I_(p) ^(c)=0.84 mAcm⁻².

Voltammogram C was recorded in the same solution of N-methylphthalimideafter the addition of approximately 10 equivalents of phenol. In markedcontrast to the reduction of the imide by itself, there is a singlereduction wave with E_(p) ^(c)=−1.64 V and I_(p) ^(c)=1.62 mA cm⁻². Thispeak current is about twice that of the one-electron process inVoltammogram B; this indicates that the single wave in Voltammogram C isa two-electron process. The difference in the peak cathodic potentialsof the first one-electron reduction in Voltammogram B and thetwo-electron reduction in Voltammogram C is 0.15 V. There is nooxidation wave on the return sweep, indicating that the productundergoes a chemical reaction following electrochemical reduction.

Controlled potential electrolysis was carried out to determine theproduct formed after electrochemical reduction in the presence ofphenol. A working electrode consisting of a glassy carbon flag (A˜2 cm²)was immersed in a [bmim][PF₆] solution containing 0.063 mol L⁻¹N-methylphthalimide (0.101 g, 6.3×10⁻⁴ mol) and 0.63 mol L⁻¹ phenol. Atwo-electron reduction of 100% reduction of the imide would require 121C of charge (Q_(Theor,100%)) to be passed during electrolysis. Aplatinum coil counter electrode was placed in a solution of pure[bmim][PF₆] separated from the bulk solution by a glass frit. Thepotential of the working electrode was held at E_(app)=−1.7 V.Electrolysis was halted after the passage of 126.0 C. Comparison of thepeak cathodic current at a glassy carbon disk working electrode before(2.25×10⁻² A cm⁻²) and after (1.12×10⁻³ A cm⁻²) electrolysis (FIG. 4)indicated that 95.0% of the N-methylphthalimide had reacted. The currentefficiency was 91.2% (Q_(Theor,95.0%)=115 C). The reaction was alsomonitored by high performance liquid chromatography (HPLC).

Thus, FIG. 5(A) is an HPLC chromatogram of a standard solutioncontaining 0.61 mol L⁻¹ phenol (Retention Time [RT]=7.1 min), 0.064 molL⁻¹ N-methylphthalimide (RT=11.8 min) and 0.063 mol L⁻¹N-methylhydroxyisoindol-1-one (RT=4.3 min). FIG. 5(B) is an HPLCchromatogram of [bmim][PF₆] ionic liquid solution (RT=1.6 min)containing 0.62 mol L⁻¹ phenol (RT=7.3 min), 0.065 mol L⁻¹ N-methylphthalimide (RT=12.4 min) before the reaction. FIG. 5(C) is an HPLCanalysis of [bmim][PF₆] ionic liquid (RT=1.4 min) solution initiallycontaining 0.063 mol L⁻¹ N-methylphthalimide and 0.63 mol L⁻¹ phenolsolution following electrolysis at an applied potential of −1.7 V(Q_(T)=126.0 C), of a solution. Thus, FIG. 5(C) indicates the presenceof phenol, N-methylphthalimide and a single product. Quantitativeanalysis of the HPLC data, indicated a molar ratio of 19.8 between theproduct and the starting material. This represents a 95:5 molar ratio,consistent with the results obtained from the CV analysis.

The product was extracted from the ionic liquid reaction mixture withdistilled water, the latter solvent forming a biphasic system with thehydrophobic ionic liquid. The extraction procedure involved shaking theionic liquid with distilled water and decanting the upper aqueous phase.Thin layer chromatography (TLC) was used to analyse the ionic liquidlayer after the extraction procedure; no product material was indicated.The aqueous washings were combined and concentrated with sodium chloridesalt. The resulting aqueous suspension was shaken with diethyl ether toextract the product. Following the extraction procedure, TLC analysis(80:20 ethyl ethanoate:petroleum ether) of the aqueous phase did notindicate the presence of product material. The diethyl ether washingswere combined and dried over magnesium sulfate. The suspension wasgravity filtered and the diethyl ether solvent evaporated to yield ared, non-viscous oil (0.32 g). The crude oil was eluted on a flashsilica column (50:50 ethyl ethanoate:hexane) and the product wasobtained as a white solid (0.038 g, yield=38%).

The product was identified as 3-hydroxy-2-methyl-isoindolin-1-one by ¹Hand ¹³C nuclear magnetic resonance spectroscopy and electrospray massspectrometry. Hence, the reduction of N-methylphthalimide to3-hydroxy-2-methyl-isoindolin-1-one has been indicated. The low yield(0.038 g, 38%) is due to the handling of such small quantities. From thequantitative HPLC results, it can now be concluded that the 95% ofstarting material, which was consumed, had been converted to the product3-hydroxy-2-methyl-isoindolin-1-one under the reaction conditions. Theabove example demonstrates that the process of the present invention maybe used to produce a clean, quantitative conversion of the organicstarting material. Furthermore, the electrochemical transformation iseffected without side reactions. Thus, the reaction mixture is virtuallyfree of side products and advantageously, the air- and moisture-stableionic liquid can be recovered for reuse.

1. A process for electrochemical transformation of an organic compoundto form a product, said process comprising the steps of: (i)electrochemically effecting said transformation of the organic compoundin the presence of an electrolyte comprising at least one roomtemperature ionic liquid to form the product, said ionic liquid beingair-stable and moisture-stable, wherein the organic compound includes atleast one structural element selected from the following: acarbon-halogen bond, a C≡C triple bond, an ester group, an ether group,a carboxylic acid group, an amido group, an imido group, —OH, —NO₂, analdehyde group and a keto group, and (ii) separating the product.
 2. Theprocess according to claim 1 further comprising the recovery of saidionic liquid.
 3. The process according to claim 1 wherein theelectrochemical transformation is an oxidation, reduction, or a coupledpair of oxidation and reduction.
 4. The process according to claim 1wherein said structural element is oxidized or reduced.
 5. The processaccording to claim 1 wherein the compound includes at least onestructural element selected from the following: NO₂, an imido group, analdehyde group and a carboxylic acid group.
 6. The process according toclaim 1 wherein the ionic liquid comprises an imidazolium, pyridinium,pyridazinium, pyrazinium, oxazolium, triazolium, pyrazolium,pyrrolidinium, piperidinium, tetraalkylammonium or tetraalkylphosphoniumsalt.
 7. The process according to claim 6 wherein the ionic liquid has amelting point of up to 40° C.
 8. The process according to claim 6wherein the ionic liquid is substantially immiscible with water.
 9. Theprocess according to claim 1 wherein the ionic liquid is an air-andmoisture stable room temperature ionic liquid selected from a compoundof formula:

wherein each R^(a) is independently selected from a C₁ to C₄₀ straightchain or branched alkyl or a C₃ to C₈ cycloalkyl group, wherein saidalkyl or cycloalkyl group which may be substituted by one to threegroups selected from: C₁ to C₆ alkoxy, C₆ to C₁₀ aryl, CN, OH, NO₂, C₁to C₃₀ aralkyl and C₁ to C₃₀ alkaryl; each R^(b), R^(c), R^(d), R^(e),R^(f), R^(g) and R^(h) is the same or different and are eachindependently selected from hydrogen or any of the R^(a) groups asdefined above; and [A]^(n−) represents an anion having a charge n−;wherein n is 1-3.
 10. The process according to claim 9 wherein the ionicliquid is an air-and moisture stable room temperature ionic liquidselected from a compound of formula:

wherein [A]^(n−), R^(a), R^(g) and n are as defined in claim
 9. 11. Theprocess according to claim 9 wherein each R^(a) represents C₁ to C₄₀straight chain or branched alkyl.
 12. The process according to claim 9wherein each R^(a) represents C₁ to C₈ straight chain or branched alkyl.13. The process according to claim 9 wherein R^(g) and R^(h) representsC₁ to C₄₀ straight chain or branched alkyl.
 14. The process according toclaim 9 wherein R^(g) and R^(h) represents C₁ to C₈ straight chain orbranched alkyl.
 15. The process according to claim 9 wherein R^(b),R^(c), R^(d), R^(e), R^(f), R^(g) and R^(h) each represents hydrogen.16. The process according to claim 9 wherein R^(a), R^(g) and R^(h) eachrepresents a C₁-C₂₀ alkyl group.
 17. The process according to claim 9wherein [A]^(n−) represents a single species of anion having valency n.18. The process according to claim 9 wherein n is
 1. 19. The processaccording to claim 9 wherein [A]^(n−) represents an anion selected from[Cl]⁻, [Br]⁻, [I]⁻, boron or phosphorus fluorides, [NO₃]⁻, [SO₄]²⁻,[HSO₄]⁻, [HCO₃]⁻, [(CF₃SO₂)₂N]⁻, [AsF₆]⁻, [SbF₆]⁻, aryl sulfonates,alkylsulfonates, mono- or difluorinated alkyl sulfonates includingperfluorinated alkylsulfonates, carboxylic acid anions, fluorinatedcarboxylic acid anions and metal halides.
 20. The process according toclaim 9 wherein [A]^(n−)represents an anion selected from [PF₆]⁻,[BF₄]⁻, [OSO₂CF₃]⁻, [OSO₂(CF₂)₃CF₃]⁻, [(CF₃SO₂)₃C]⁻, [CH₃CH₂SO₃]⁻,[OCO₂CF₃]⁻, [OCO₂(CF₂)₃CF₃]⁻, [OCO₂CH₃]⁻, nitrate, sulfate,hydrogensulfate, hydrogencarbonate, acetate, trifluoroacetate, lactate,[(CF₃SO₂)₂N]⁻,[B(alkyl)₄]⁻wherein each alkyl is the same or differentand is any straight chain or branched C₁ to C₁₀ alkyl group, [SbF₆]⁻ and[AsF₆]⁻.
 21. The process according to claim 9 wherein [A]^(n−)represents an anion selected from [PF₆]⁻, [BF₄]⁻ and [(CF₃SO₂)₂N]⁻. 22.The process according to claim 1 wherein the ionic liquid is1-butyl-3-methylimidazolium hexafluorophosphate orN-butyl-N-methyl-pyrrolidinium bis(trifluoromethanesulfonyl)imide. 23.The process according to claim 1 wherein the electrochemicaltransformation is carried out in the presence of a proton source. 24.The process according to claim 23 wherein the proton source is selectedfrom phenol, a mineral acid, an organic acid, a conjugate acid of theanion A, or water.
 25. The process according to claim 23 wherein theproton source is phenol.
 26. The process according to claim 1 whereinthe electrochemical transformation is conducted at a temperature withinthe molten range of the electrolyte.
 27. The process according to claim1 wherein the product formed by the transformation is separated from theionic liquid by solvent extraction, distillation, precipitation or as animmiscible liquid layer.
 28. The process according to claim 1 whereinthe ionic liquid is reusable after recovery of the product.
 29. Theprocess according to claim 1 wherein the ionic liquid is reusabledirectly after recovery of the product.
 30. A process according to claim1 wherein the organic compound is N-methylphthalimide, thetransformation is reduction, and the ionic liquid is1-butyl-3-methylimidazolium hexafluorophosphate.